E3 ubiquitin-protein ligase, which catalyzes ubiquitination of target proteins together with ubiquitin-conjugating enzyme E2 UBE2L3. Acts as an atypical E3 ubiquitin-protein ligase by working together with cullin-RING ubiquitin ligase (CRL) complexes and initiating ubiquitination of CRL substrates: associates with CRL complexes and specifically mediates addition of the first ubiquitin on CRLs targets. The initial ubiquitin is then elongated by CDC34/UBE2R1 and UBE2R2. E3 ubiquitin-protein ligase activity is activated upon binding to neddylated cullin-RING ubiquitin ligase complexes. Plays a role in protein translation in response to DNA damage by mediating ubiquitination of EIF4E2, the consequences of EIF4E2 ubiquitination are however unclear. According to a report, EIF4E2 ubiquitination leads to promote EIF4E2 cap-binding and protein translation arrest. According to another report EIF4E2 ubiquitination leads to its subsequent degradation. Acts as the ligase involved in ISGylation of EIF4E2. In vitro, controls the degradation of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex member SUN2 and may therefore have a role in the formation and localization of the LINC complex, and as a consequence, nuclear subcellular localization and nuclear morphology.